Showing papers on "Total synthesis published in 1993"
TL;DR: The first synthesis of the macrolide insecticide A83543A (lepicidin A) has been completed using a Diels-Alder strategy to construct the carbocyclic framework.
Abstract: The first synthesis of the macrolide insecticide A83543A (lepicidin A) has been completed using a Diels-Alder strategy to construct the carbocyclic framework. Diene synthesis through Pd-catalyzed Stille coupling of a macrocyclic vinylstannane and suitably functionalized vinyl iodide was followed by a diastereoselective Lewis acid-mediated intramolecular Diels-Alder reaction to construct the trans hydrindene subunit. Refunctionalization and intramolecular aldol condensation afforded the differentially protected (+)-lepicidin A aglycon. Successive glycosidations with 2,3,4-tri-O-methyl-D-rhamnose and N-protected L-forosamine followed by deprotection and methylation completed the synthesis of the enantiomer of the natural product
267 citations
TL;DR: The first total synthesis of rapamycin (1) in its naturally occurring enantiomeric forms was reported in this article, where the bridging unit, enedistannane 3,5 was expected to bring together the two terminal vinyl iodides of precursor 2 in a Stille-t~pe6.
Abstract: Rapamycin (1)lJ is a novel, naturally occurring substance, with potent antibiotic, cytotoxic, and immunosuppressive activity. Isolated from Streptomyces hygroscopicus found in an Easter Island soil sample, this synthetically challenging molecule is currently under intense investigation as a rival to the immunosuppressive agents FK506 and cyclo~porin.~ Herein we report the first total synthesis of rapamycin (1) in its naturally occurring enantiomeric forms4 Rapamycin (1) with its 31-membered ring, plethora of asymmetric and geometrical centers, and sensitive functionality presents to thesyntheticchemist a formidablechallenge. A rather daring approach to this target is outlined in Scheme I. According to this strategy, rapamycin (1) was to be constructed by a single operation from a fully functionalized acyclic precursor (2), via a “stitching-cyclization” process that would bring in the two missing carbons as the central olefinic unit (C19420) of the triene moiety. The bridging unit, enedistannane 3,5 was expected to bring together the two terminal vinyl iodides of precursor 2 in a Stille-t~pe6.~ coupling-cyclization reaction to furnish the natural product in a single step. Such a strategy would ensure a direct approach to 1 and avoid instability problems, deprotection steps, and late stage oxidation state adjustments. Precursor 2 was expected to be derived from advanced key intermediates 4 and 5 (Scheme I). Coupling of advanced intermediates 48 and 59 in the presence of 1 -hydroxybenzotriazole and diisopropylcarbodiimide proceeded
228 citations
TL;DR: In this article, the total synthesis of the HMG-CoA synthase inhibitor 1233A (1) starting from either (R)-pulegone (6) or diketo ester 12, is described.
Abstract: The total synthesis of the HMG-CoA synthase inhibitor 1233A (1), starting from either (R)-pulegone (6) or diketo ester 12, is described. The key transformations included the diastereoselective [2,3] rearrangements of allylic ethers 9 and 19 to alcohols 10 and 11b, respectively, and the diastereoselective hydroboration of 11b to form 19. A Pd-mediated coupling of iodo olefin 31a with tert-butyl crotonate under newly devised conditions provides an efficient preparation of the diene portion of 1233A
216 citations
Book•
29 Jun 1993
TL;DR: This paper presents the first total Synthesis of several Natural Products Based On Alkyne-Co2(Co2)6 Complexes, and discusses the design and synthesis of Cooperative "Pinwheel" Fluorescent Sensors, and the application of Silicon-Ass Intramolecular Cross-Coupling.
Abstract: Chapter 1. The Total Synthesis Of Luzopeptins. Chapter 2. Synthesis of Geldanamycin Using Glycolate Aldol Reactions. Chapter 3. From Methylene Bridged Glycoluril Dimers To Cucurbit[N]Uril Analogs With Some Detours Along The Way. Chapter 4. Application Of Silicon-Assisted Intramolecular Cross-Coupling In Total Synthesis Of (+)-Brasilenyne. Chapter 5. Samarium(II) Promoted Ketyl Olefin Cyclizations Applied To The Total Syntheses Of (-)-Steganone And (+)-Isoschizandrin. Chapter 6. The Synthesis Of Polycavernoside A. An Example Of Conformationally Guided Macrolactonization. Chapter 7. First Total Synthesis Of Several Natural Products Based On Alkyne-Co2(Co)6 Complexes. Chapter 8. Total Synthesis Of Myriaporones 1, 3, and 4. Chapter 9. Adventures In Natural Product Synthesis: From Deep Sea Sponge To Pilot Plant. The Large Scale Total Synthesis Of The Marine Natural Product (+)-Discodermolide. Chapter 10. Synthesis Of Aprepitant. Chapter 11. Total Synthesis And Mechanism Of Action Studies On The Antitumor Alkaloid,(-)-Agelastatin A. Chapter 12. Design And Synthesis of Cooperative "Pinwheel" Fluorescent Sensors. Chapter 13. Functionalization Of Pyridines And Thiazoles Via The Halogen-Dance Reaction, Application To The Total Synthesis Of Caerulomycin C And WS75624 B. Chapter 14. Diastereoselective Intramolecular 4+3 Cycloaddition And An Enantioselective Total Synthesis Of (+)-Dactylol.
175 citations
01 Jan 1993
TL;DR: The use of carbohydrates as chiral starting materials for the synthesis of enantiomerically pure natural products and the development of peptide-based pharmaceuticals.
Abstract: 1 Carbohydrates- 11 Introduction- 12 Recent developments in O-glycosidation methodology- 13 Recent developments in C-glycoside synthesis- 14 Synthesis of antibiotic sugars- 15 Use of carbohydrates as chiral templates and reagents for asymmetric synthesis- 151 Asymmetric reduction- 152 Enantioselective alkylation of carbohydrate derived nucleophiles- 153 Enantioselective alkylation of carbohydrate derived electrophiles- 154 Monosaccharides as chiral auxiliaries for cycloaddition reactions- 16 Use of carbohydrates as chiral starting materials for the synthesis of enantiomerically pure natural products- References- 2 Aromatic compounds- 21 Introduction- 22 Benzenoids- 23 Coumarins- 24 Isocoumarins, chromanones, chromones and cannabinoids- 25 Macrocyclic lactones- 26 Pyrones, butenolides, lignans and benzofurans- 27 Terphenyls- 28 Flavonoids- 29 Xanthones and benzophenones- 210 Naphthalenes and naphthoquinones- 211 Anthraquinones- 212 Anthracyclines- 213 Some other polycyclic antibiotics- 214 Ansamycins- References- 3 Terpenoids- 31 Introduction- 32 Monoterpenoids- 33 Sesquiterpenoids- 34 Diterpenoids- 35 Sesterterpenoids- 36 Triterpenoids- 37 Carotenoids- References- 4 Steroids- 41 Introduction- 42 Molecular rearrangement- 43 Remote functionalisation- 44 Photochemical reactions- 45 Partial synthesis- 451 Oestranes- 452 Androstanes- 453 Pregnanes- 454 Cholanes- 455 Cardenolides and bufadienolides- 456 Vitamins D- 457 Cholestanes and derivatives- References- 5 Amino acids, peptides and proteins- 51 Introduction- 52 Amino acids- 521 Synthesis- 522 New naturally occurring amino acids- 53 Peptides- 531 Synthesis- 532 Synthesis of glycopeptides- 533 Synthesis of phosphorylated peptides- 534 Post-translational modifications- 535 Design of peptide-based pharmaceuticals- 536 New peptides from natural sources- 54 Techniques for structural elucidation- 541 X-ray crystallography- 542 Nmr spectroscopy- 543 Molecular modelling- 55 Proteins- 551 Incorporation of unnatural amino acids- 552 Purification and analysis- 553 Sequences, databases and protein folding- 56 Appendix- 561 Useful books- 562 Databases- References- 6 Alkaloids- 61 Introduction- 62 Biomimetic studies- 621 Biomimetic synthesis of Iboga and Aspidosperma alkaloids- 622 Biomimetic routes to Daphniphyllum alkaloids- 63 Synthesis- 631 Reserpine- 632 Other yohimbine and heteroyohimbine alkaloids- 64 Marine alkaloids- 641 The manzamines- 642 Biosynthetic origin of manzamines- 643 Total synthesis of manzamine C- 644 Synthetic approaches to manzamine A- References- 7 Nucleosides, nucleotides and nucleic acids- 71 Introduction- 72 Nucleosides- 721 Nucleoside synthesis: general methods- 722 Nucleosides containing modified sugars- 723 Other nucleosides of interest- 724 Some useful and novel reactions- 73 Nucleotides- 731 Nucleoside monophosphates and their analogues- 732 Cyclic nucleotides- 733 Nucleoside polyphosphates and their analogues- 74 Nucleic acids- 741 Oligodeoxyribonucleotide synthesis- 742 Oligoribonucleotide synthesis- 743 Oligonucleotides containing modified internucleotidic links- 744 Nucleic acid sequencing- 75 Supplementary reading- References- 8 Porphyrins- 81 General introduction- 82 Macrocycle biosynthesis- 821 Introduction- 822 Substitution pattern of uroporphyrinogen III- 823 Biosynthesis of vitamin B12- 83 Haemoprotein model compounds- 831 Introduction- 832 Supramolecular effects in haemoprotein model compounds- 833 Cytochrome P-450 models- 84 Porphyrins with easily oxidisable substituents- 841 Introduction- 842 Mesotetrakis (3,5-di-t-butyl-4-hydroxyphenyl)porphyrin- 843 Mesotetrakis (pyrogallyl) porphyrin- 85 Utilisation of porphyrin excited states- 851 Introduction- 852 Modelling photosynthesis- 853 Solar energy conversion- 86 Porphyrins in photodynamic therapy- 861 Introduction- 862 Haematoporphyrin derivative, HpD- 863 Second generation porphyrins- 864 New approaches to photosensitiser delivery- 865 Mechanism of photodynamic action- 866 Photosensitising porphyrins as herbicides- 87 DNA-porphyrin interactions- 871 Introduction- 872 DNA cleavage- 873 DNA binding- 88 Porphyrins as novel materials- 881 Introduction: solid state and liquid crystalline phenomena- 882 Porphyrins in molecular electronics- 89 Porphyrins with liquid crystalline properties- 891 Introduction- 892 Porphyrins with discotic phases- References- 9 Aliphatic compounds- 91 Introduction- 92 Semiochemicals- 921 Lepidopteran pheromones- 922 Methyl substituted aliphatic pheromones- 923 Unbridged spiroketals- 93 Development of synthetic technology- 931 Bridged spiroketal semiochemicals of bark beetles- 932 Organosulphur semiochemicals- 94 Marine natural products- 941 Palytoxin- 942 Okadaic acid, dinophysistoxins and acanthifolicin- 943 Fused ring polyethers- 95 Enyne-allene and enediyne antibiotics- 951 Neocarzinostatin- 952 Trisulphide triggered enediyne antibiotics: the esperamicins and calicheamicins- 953 Dynemicins- References- Chemical abbreviations and acronyms
157 citations
148 citations
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135 citations
TL;DR: An efficient total synthesis of (+)-preussin, (25,3S,SR)-1-methyl-5-nonyl-2-(phenylmethyl)-3-pyrrolidinol (1), was achieved by way of a convergent, intramolecular imidotitanium-alkyne [2+2] cycloaddition-acyl cyanide condensation sequence as discussed by the authors.
Abstract: An efficient stereoselective total synthesis of (+)-preussin, (25,3S,SR)-1-methyl-5-nonyl-2-(phenylmethyl)-3-pyrrolidinol (1), was achieved by way of a convergent, intramolecular imidotitanium-alkyne [2+2] cycloaddition-acyl cyanide condensation sequence
134 citations
128 citations
TL;DR: The first total synthesis of the calicheamicin γ 1 I oligosaccharide fragment in the form of its methyl glycoside has been achieved by as discussed by the authors, which was initially worked out on a model for the ABC-ring system and then successfully applied to the real system.
Abstract: The first total synthesis of the calicheamicin γ 1 I oligosaccharide fragment in the form of its methyl glycoside (62) has been achieved. The synthetic challenge of the B-ring was recognized and studied initially, resulting in a novel and unique solution to the stereochemical problems posed involving a [3,3]-sigmatropic rearrangement of an allylic thionoimidazolide (111). This chemistry was initially worked out on a model for the ABC-ring system (47) and then successfully applied to the real system. The success of this synthesis has enabled the completion of the first synthesis of the natural product itself, calicheamicin γ 1 I (I), as will be described in the following papers in this issue
TL;DR: In this paper, a total synthesis of the potent non-opiate analgesic alkaloid epibatidine is described, in which the key step is a reductive palladium-catalysed Heck-type coupling.
TL;DR: The convergent stereocontrolled, asymmetric total synthesis of (+)-paraherquamide B is described in this paper, where an improved procedure to effect reduction of unprotected oxindoles to indoles is presented.
Abstract: The convergent stereocontrolled, asymmetric total synthesis of (+)-paraherquamide B is described. Key features of this synthesis include (1) an improved procedure to effect reduction of unprotected oxindoles to indoles; (2) a complex application of the Somei/Kametani coupling reaction; (3) a high-yielding and entirely stereocontrolled intramolecular SN2‘ cyclization reaction that constructs the core bicyclo[2.2.2] ring system; (4) a mild Pd(II)-mediated cyclization reaction that constructs a complex tetrahydrocarbazole; and (5) the chemoselective reduction of a highly hindered tertiary lactam in the presence of an unhindered secondary lactam, utilizing precoordination of the more reactive secondary lactam to triethylaluminum.
01 Jan 1993
TL;DR: Progress in the Total Synthesis of Spirotetronic Acid Macrolide Antibiotics and Convergent Stereospecific Total Syntheses of Monocillin I and Monorden are reported.
Abstract: Cyclization Methods Related to the Synthesis of Macrolide Antibiotics.- Progress in the Total Synthesis of Spirotetronic Acid Macrolide Antibiotics.- Convergent Stereospecific Total Synthesis of Monocillin I and Monorden (or Radicicol).- Recent Progress in the Chemical Modification of Erythromycin.- Chemistry of FK - 506.- The "Enediyne" Antibiotics Calicheamicin ?1I, Esperamicin-Ar and Dynemicin-A: Physicochemical and Biological Properties-Partial and Total Synthesis.- Synthesis and Chemistry of Neocarzinostatin Analogs.- Synthesis of Nogalamycin and Related Substances.- Total Synthesis of Aryl C-Glycoside Antibiotics.- Total Synthesis of the Antifungal Antibiotic Ambruticin.- Synthetic Approaches to Methylenomycin B and Analogs.- The Orthosomycin Antibiotics.- ? -Unsubstituted ? -Lactams as Synthons for Antibiotics.- Chemistry and Synthesis of some Novel ? -Lactam Antibiotics and ? -Lactamase Inhibitors.- Recent Advances in the Chemistry and Biochemistry of ? -Lactams as ? -Lactamase Inhibitors.- Chemistry of Biologically Important Hydroxylated Indolizidines Synthesis of Swainsonine, Castanospermine and Slaframine.- The Chemistry and Total Synthesis of Mevinolin and Related Compounds.- Synthetic Efforts Towards Cerulenin and Tetrahydrocerulenin.
TL;DR: An application to the total synthesis of rebeccamycin is described, whereodium salts of indoles have been found to open α-1,2-anhydrosugars with inversion yielding indole-β-N-glycosides.
Abstract: Sodium salts of indoles have been found to open α-1,2-anhydrosugars with inversion yielding indole-β-N-glycosides. This methodology constitutes a concise route from glycals to the biologically active indole-N-glycosides. An application to the total synthesis of rebeccamycin is described
TL;DR: The first total synthesis of calicheamicin γ 1 I (1) has been achieved in this paper, where the stereoselective reduction of oxime 31, obtained from the coupling product with NaCNBH 3 in the presence of BF 3 -OEt 2, late in the synthetic scheme, generated the desired alkoxylamine 32 and its A-4 isome 32-epi
Abstract: The first total synthesis of calicheamicin γ 1 I (1) has been achieved. The stereoselective glycosidation, joining the appropriately functionalized aglycon 3 with the oligosaccharide fragment 2, was realized uding Schmidt's trichloroacetimidate methodology. Segment 4, equipped with the photolabile 2-nitrobenzyl group at the reducing end, was synthesized using similar chemistry to that applied to the synthesis of its methyl glycoside counterpart (see accompanying paper). Stereoselective reduction of oxime 31, obtained from the coupling product, with NaCNBH 3 in the presence of BF 3 -OEt 2 , late in the synthetic scheme, generated the desired alkoxylamine 32 and its A-4 isome 32-epi
TL;DR: The total synthesis of hemibrevetoxin B (1) and (7aα)-epi-hemibrevoxin B(2) is described in this article, where the α-vinyl functionality was installed using the Eschenmoser's salt methodology.
Abstract: The total synthesis of hemibrevetoxin B (1) and (7aα)-epi-hemibrevetoxin B (2) is described. The synthesis of the epimer (2) was achieved through a convergent approach involving coupling of the carboxylic acid 17 carrying the bicyclic pyran system with the hydroxy compound 31 containing the monocyclic pyran system, thionation of the resulting diester 32 to the dithionoester 33, photolytic closure to the oxepane enol ether 34, and hydroxy ketone cyclization to the dioxepane system 40. The Z-diene system was established using a selenyl-Wittig reaction followed by syn elimination of the selenoxide to the diene. The α-vinyl functionality was installed using the Eschenmoser's salt methodology. The synthesis of hemibrevetoxin B (1) was achieved through a linear approach involving sequential formation of the oxepane rings (65 → 67 → 73) using the method of thionolactone formation followed by nucleophilic addition and regio/stereoselective hydroboration (67 → 68, 75 → 76). Elaboration of the side chains was carried out in a similar fashion as described for the epimer. The streochemistry of the ring junctures in 1 and 2 and intermediates leading to them was established by X-ray cristallographic analysis carried out on compounds 45 and 54
TL;DR: The stereocontrolled total synthesis of the novel analgesic agent (-)-epibatidine and its enantiomer starting with 6-chloropyridine-3-carboxaldehyde has been carried out by way of intermediates 3-10 as discussed by the authors.
Abstract: The stereocontrolled total synthesis of the novel analgesic agent (-)-epibatidine (1) and its enantiomer starting with 6-chloropyridine-3-carboxaldehyde (2) has been carried out by way of intermediates 3-10
TL;DR: The first total synthesis of racemic indolizomycin (1) has been achieved as discussed by the authors, via stereospecific intramolecular vinylsilane/carbinol amide cyclization (15→16), rhodium(II) acetate mediated diazoacetate insertion into thioamide 17, and epoxide introduction (25→27→29).
Abstract: The first total synthesis of racemic indolizomycin (1) has been achieved. Initial investigations provided the functionalizcd indolizidine, 31, via (i) stereospecific intramolecular vinylsilane/carbinol amide cyclization (15→16), (ii) rhodium(II) acetate mediated diazoacetate insertion into thioamide 17, and (iii) epoxide introduction (25→27→29). Although subsequent attempts to fully elaborate 31 into indolizomycin were unsuccessful, these experiments formed the basis of a revised route which did ultimately produce the natural product
TL;DR: The synthesis of human insulin, a two-chain peptide containing three disulfide bonds, was achieved unambiguously by sequential and selective formation in the protein for the first time as mentioned in this paper.
Abstract: Total synthesis of human insulin, a two:chain peptide containing three disulfide bonds, was achieved unambiguously by sequential and selective formation of disulfide bonds in the protein for the first time. The key reaction in the synthesis is separate regioselective formation of three disulfide bonds using a silyl chloride method developed by us. Prior to the insulin synthesis, it was confirmed by the syntheses of double-disulfide peptides, conotoxin M1, β-hANP, and an unnatural parallel dimer of α-hANP, that no disulfide exchange occurred during the silyl chloride treatment. Using three orthogonal thiol-protecting groups, Trt, Acm, and t-Bu, the three disulfide bonds of human insulin were efficiently constructed by successive reactions using thiolysis, iodine oxidation, and the silyl chloride method
TL;DR: A racemic mixture of epibatidine, a potent analgesic alkaloid possessing a 7-azanorbornane structure, has been synthesized via a versatile four-step synthetic route as mentioned in this paper.
TL;DR: The first enantioselective total synthesis of (-)-calicheamicinone (3), the naturally occurring antipode of the calicheamin aglycon, has been achieved as discussed by the authors.
Abstract: The first enantioselective total synthesis of (-)-calicheamicinone (3), the naturally occurring antipode of the calicheamicin aglycon, has been achieved
TL;DR: The structurally unique antifungal and antitumor antibiotic aranorosin was prepared in a convergent, stereoselective sequence and the corrected [α] D strongly indicated the (6'R)-stereochemistry for the natural compound.
Abstract: The structurally unique antifungal and antitumor antibiotic aranorosin was prepared in a convergent, stereoselective sequence. Oxidative cyclization of N-protected L-tyrosine, followed by face-selective 1,2-addition of [(benzyloxy)methyl]lithium, Henbest oxidation in the presence of Kishi's radical inhibitor, and simultaneous N,O-deprotection led to an amino diol which was N-acylated with the fatty acid side-chain segment. After a low-temperature reduction of the lactone moiety to the lactol, the carbonyl function was regenerated under neutral conditions by diol cleavage with sodium periodate. Preparation of the acid side chain involved a diastereoselective imide α-alkylation directed by Evans' oxazolidinone auxiliary, followed by a series of Wittig-Horner chain extensions. Since the relative configuration at the C(6') position of the natural product had not been determined, we prepared both the (6'S) and the (6'R) isomers of aranorosin. Comparison of synthetic material with the reported spectral data for natural (-)-aranorosin, especially 1 H and 13 C NMR and [α] D , did not allow a definitive assignment. After purification of a sample of the isolated material from pseudoarachniotus roseus, the corrected [α] D strongly indicated the (6'R)-stereochemistry for the natural compound. This assigment was confirmed by circular dichroism spectra for (6'S)- and (6'R)-aranorosin and the natural material
TL;DR: An efficient, sterocontrolled entry to the dioxabicyclo[3.3.0] octane ring system of (±)-kumausalkene has been developed as discussed by the authors.
Abstract: An efficient, sterocontrolled entry to the dioxabicyclo[3.3.0]octane ring system of (±)-kumausalkene has been developed. This synthesis buids upon our general strategy for preparing C 15 halogenated tetrahydrofuranoid marine lipids using the ring-enlarging tetrahydrofuran annulation of cyclic, allylic diols as the central step. A key intermediate, hydrobenzofuranone 8, is available with complete sterocontrol form the Lewis acid-catalized condensation of 1-vinylcyclopentanediol (4) and α-(benzoyloxy)acetaldehyde (Scheme II)
TL;DR: A convergent synthesis of a protected version of (+)-lycoricidine has been accomplished in 13 steps from L-arabinose as mentioned in this paper, using a novel N-sulfonyliminium ion cyclization of vinylsilane aldehyde.
Abstract: A convergent synthesis of a protected version of (+)-lycoricidine has been accomplished in 13 steps from L-arabinose. Preparation of the aminocyclitol moiety 50 employed a novel vinylsilane-terminated N-sulfonyliminium ion cyclization of vinylsilane aldehyde 42. Closure of the B-ring using an intramolecular Heck reaction afforded lycoricidine derivative 58. An unexpected cyclization of vinylsilane aldehyde 42 allowed for the stereodivergent preparation of semiprotected conduritols 43 and 45
TL;DR: In this article, a short-step synthesis of (−)-pumiliotoxin C was demonstrated by using RuH 2 (PPh 3 ) 4 catalyst to give the corresponding amides.
TL;DR: The total synthesis of the structurally novel tetraquinane diterpenoid (±)-crinipellin B (4) has been accomplished via a 22-step sequence of reactions.
Abstract: Beginning with 2-methyl-2-cyclopenten-1-one (d), the total synthesis of the structurally novel tetraquinane diterpenoid (±)-crinipellin B (4) has been accomplished via a 22-step sequence of reactions